Medications to Treat Alcohol Dependence: Title and subTitle BreakAdding to the Continuum of Care

The most prevalent form of treatment for alcohol dependence in the United States is group counseling and referral to community support groups, a treatment that was developed more than 30 years ago.¹ At that time, the only medication available to prevent relapse was disulfiram, which has limited efficacy and patient acceptability. Since that time, acamprosate and naltrexone have been approved for the treatment of alcohol dependence, the latter in both oral and long-acting injectible forms. However, few physicians prescribe these drugs, and most treatment programs do not use them.²

In this issue of JAMA, Johnson and colleagues³ report on a large multisite trial of topiramate, a drug with complex actions including activity at γ-aminobutyric acid and glutamate receptors. Replicating the results of a smaller randomized controlled trial,⁴ topiramate produced significant and meaningful improvement in a wide variety of drinking outcomes. At the end of the 14-week trial, differences between topiramate and placebo were still increasing, suggesting that even more improvement may occur with longer administration. In contrast to other medications, patients were not required to stop drinking prior to study entry. Behavioral support was minimal, focusing on enhancing compliance and encouraging abstinence.

The Combined Pharmacotherapies and Behavioral Interventions (COMBINE) trial⁵ found that oral naltrexone with brief behavioral support was at least as effective as specialized outpatient alcohol counseling alone, and long-acting naltrexone for injection had similar results with a slightly different behavioral platform.⁶ In a new analysis of 2 naltrexone trials, both of which were reported as negative on their primary outcome analyses, Gueorguieva et al⁷ found substantially improved odds of following an abstinent trajectory among naltrexone patients, suggesting that effect size may be minimized with comparisons of means alone. Taken together, these studies provide strong support that for many patients, combining medication with brief behavioral support is an effective alternative to group-based counseling. What patients with alcohol dependence now need is ready access to these medications, coupled with an effective behavioral platform.

One potential solution is for primary care physicians and psychiatrists to begin systematically identifying and treating alcohol dependence in their patients. Unfortunately, physicians receive minimal education in this area, being exposed primarily to hospitalized, severely ill patients with alcoholism. Consequently, many clinicians may feel ill-equipped to care for patients with alcohol disorders, except to refer to specialty treatment. However, access to specialized treatment has become more difficult in the last decade, and although the prevalence of alcohol use disorders has not changed substantially, even fewer patients receive treatment than did 10 years ago.⁸ Furthermore, most specialty programs are now staffed by nonmedical counselors, and physicians have not been fully integrated into the treatment process after the completion of withdrawal.

Recent epidemiological research demonstrates that alcohol dependence is primarily a disorder of youth, with an average age of onset of 21 years.⁹ In most cases, the disorder is episodic rather than chronic and unrelenting; almost three-quarters of patients with alcohol dependence only have 1 episode, and the average length of the longest episode is about 5 years.⁸ Those with more than 1 episode have an average of 5 episodes, with the length of episodes decreasing over time.⁸ Not only do most patients recover, most do so without receiving specialty treatment or attending support groups.¹⁰ Only the most severely and chronically affected seek specialty treatment.¹¹ For those who do receive treatment but do not respond, or who relapse, disease management approaches are effective, at least for patients with serious comorbid conditions.¹² This heterogeneity among patients who meet criteria for alcohol dependence suggests that different treatment strategies, including medications, will need to be tailored to specific populations.

Importantly, most pharmacotherapy trials for treating alcohol dependence recruit patients through newspaper advertisements. Patients responding to such advertisements are different from patients seeking specialty treatment, in particular because they are usually not overtly coerced by the criminal justice system or employers, as many patients in specialty treatment are. Also, most patients with severe comorbidities are excluded. Thus, the samples recruited for most studies resemble patients likely to be seen in primary care or psychiatric care settings, as opposed to patients in specialty treatment. This suggests that these settings may be the ideal place to implement pharmacotherapy with brief behavioral support.

Alcohol dependence is the third leading modifiable cause of death in the United States, accounting for about 85 000 deaths per year.¹³ Reducing incidence, shortening the course, and reducing the severity of episodes are valuable and important goals. Reducing the public health burden will involve addressing the needs of a broader range of patients than can be treated by the specialty treatment system. In particular, it will be important to reduce disability caused by currently untreated episodes of dependence among those with the nonrelapsing form of the illness.

By historical standards, the pace of medication development for treating this disorder is increasing, and a variety of medications with different modes of action are now available. A solid understanding of the neurobiology of alcohol addiction is providing the framework for multiple avenues of further medication development. The behavioral platform required to support medication treatment is similar to that for depression, attention-deficit/hyperactivity disorder, diabetes, and other chronic illnesses, and thus could potentially fit into general medical practice.

The primary care and mental health care systems provide an existing structure through which effective treatment could be made available to large numbers of patients with alcohol dependence who are not currently receiving any treatment, especially those who have the nonrelapsing form of the illness. The National Institute on Alcohol Abuse and Alcoholism has published a recently updated clinician's guide for primary care and mental health clinicians.¹⁴ The guide provides tools for rapid screening, assessment, and management of at-risk drinking and alcohol use disorders, including information on pharmacotherapy and how to provide brief behavioral support to such patients. Of course, not all patients will respond. For patients with severe, relapsing or chronic disorders, specialty addiction treatment, especially the medical component, is needed. These patients often have serious coexisting physical and mental disorders that require disease management that integrates multiple approaches. Expanding the numbers of physicians specializing in addiction medicine and psychiatry is essential, as is research on effective disease management models. The first step in this process, however, will be for all physicians to begin to see alcohol dependence as a disorder they can and should treat, and treat effectively.